Putative Structural and Functional Coupling of the Mitochondrial BKCa Channel to the Respiratory Chain

In recent years, a number of potassium channels present in the inner membrane of mitochondria have been discovered. Their physiological roles are still unclear. However, it has been observed that potassium channels affect mitochondrial matrix swelling, regulate the concentration of reactive oxygen species, change the mitochondrial membrane potential, and transport calcium into mitochondria. Additionally, it has been shown that activation of mitochondrial potassium channels protects against necrotic and apoptotic cell death during myocardial infarction or cerebral hypoxia. These findings stimulated an intensive study of the pharmacology of mitochondrial ion channels and contributed to the development of many hypotheses concerning the role of mitochondrial ion channels in cell death.
In our study, we described pharmacological and electrophysiological properties of the large-conductance Ca2+-regulated potassium channel (mitoBKCa channel) using patch-clamping mitoplasts isolated from the astrocytoma cell line. Western blot analysis, immuno-gold electron microscopy, high-resolution immunofluorescence assays and polymerase chain reaction demonstrated the presence of the BKCa channel in the inner mitochondrial membrane of the human astrocytoma cells. Also, we showed that substrates of the respiratory chain decrease the activity of the channel at positive voltages. This effect was abolished by inhibitors of the respiratory chain. Our findings indicate possible structural and functional coupling of the mitoBKCa channel with the mitochondrial respiratory chain in human astrocytoma U-87 MG cells.

06 November 2013